SUPPLEMENTAL DIGITAL MATERIAL
Demographic table
Author(Year) / Study design / Population / Purpose / Inclusion/exclusion / Treatment or risk factor / How ASP defined
and classified
RCTs comparing Bryan disc to fusion
Sasso (2011) / Randomized controlled trial
31 investigational sites
1:1 randomization
Conflict:
One or more of the authors received payments or services in support of this work, has had a financial relationship in the 36 months prior to submission of this work with an entity in the biomedical arena that could be perceived to influence what is written in this work, or has engaged in another activity that could be perceived influence what is written in this work. / N = 463
Male: 48%
Mean age: 44.6 (range 25-78) years
F/U:
68.9% (319/463)
Length of F/U:
48 months / Evaluate
clinical functional outcomes four years after either Bryan cervical
disc arthroplasty or anterior cervical discectomy and fusion,
with an emphasis on assessing any deterioration in outcomes overtime. / Inclusion: Age ≥21 years; single level cervical degenerative disc disease causing radiculopathy or myelopathy from C3-C7; failure of conservative care for 6 weeks (except myelopathy cases needing immediate attention); NDI ≥30%.
Exclusion: Presence of moderate to advanced spondylosis; radiographic signs of subluxation (>3.5mm) or angulation (11°); marked reduction or absence of motion or collapse of the intervertebral disc space > 50% normal height; facet joint arthrosis; segmental instability or cervical kyphosis; active infection; metabolic bone disease; known allergy to titanium, polyurethane, or ethylene oxide residuals; concomitant conditions requiring steroid treatment; diabetes mellitus; extreme obesity; pregnancy; inflammatory spondyloarthropathies such as ankylosing spondylitis or rheumatoid arthritis; previous cervical spine surgery. / •Arthroplasty and insertion of Bryan disc (n=242 enrolled; n=230 at 24 months; n=181 at 48 months)
•ACDF with an allograft and single anterior cervical titanium alloy plating system (n=221 enrolled; n=194 at 24 months; n=138 at 48 months) /
- RASP: NR
- CASP: NR
- CASP requiring treatment:
Zhang (2011) / Randomized controlled trial
1:1 randomization
3 sites in China
Conflict: NR / N = 109
Male: 55.8%
Mean age: TDR=44.8±5.6 (range 32-59) yrs;
ACDF=45.6±5.8 (range 31-62) yrs
F/U: 90.8% (109/120)
Length of F/U:
24 months / Compare clinical and radiographic outcomes of cervical disc arthroplasty with those of ACDF in a Chinese population / Inclusion: Followed inclusion/exclusion criteria of US FDA IDE study (Anderson/ Sasso). Symptomatic mild degenerative disc disease at one cervical level; disc herniation with radiculopathy caused by foraminal osteophytes, soft disc herniation, or myelopathy; no response to ≥ 6 weeks of treatment.
Exclusion: Axial neck pain as a solitary symptom; contraindications for TDR, including incompetent posterior elements, instability or severe facet arthrosis; insufficient cervical motion at the index level; bridging osteophytes; collapse of intervertebral disc space of > 50% of normal height; severe osteoporosis / •C-TDR with Bryan disc (n=60 enrolled; n=56 at F/U)
•ACDF (n=60 enrolled; n=53 at F/U) /
- RASP: NR
- CASP: NR
- CASP requiring treatment: Reported reoperations due to CASP
RCT comparing Prestige disc to fusion
Burkus (2010) / Randomized controlled trial
32 US investigational sites
1:1 randomization
Conflict:
“Authors have received or will receive benefits for personal and/or professional use from Medtronic Sofamor Danek in relation to products named in this article.” / N = 541
Male: 46.2%
Mean age: Prestige=43.3 (range 25-72) years; ACDF=43.9 (range 22-73) years
F/U:
50.1% (271/541)*
Length of F/U:
60 months / Burkus:Investigate the long-term safety and efficacy of the Prestige disc at 5-years in patients undergoing single-level anterior cervical discectomy and disc arthroplasty with Prestige compared to patients underoing single-level fusion. / Inclusion: Age >18 years, single-level symptomatic degenerative disc disease from C3-C7 and intractable radiculopathy and/or myelopathy; NDI scores≥30;
numeric neck pain scores ≥ 20;≥6 wk h/o neck and arm pain recalcitrant to nonoperative treatment; surgery performed in <6 weeks in patients experiencing progressive neurological worsening despite nonoperative treatment; dynamic radiography and MRI or CT myelography revealed evidence of single-level cervical disc disease and preserved motion at symptomatic level; all patients were candidates for single-level ACDF.
Exclusion:Multilevel
symptomatic DDD or evidence of cervical instability on flexion–extension radiographs, sagittal-plane translation >3.5 mm or sagittal-plane angulation >20° at a single level; symptomatic C2–3 or C7–T1 disc disease; previous surgery at involved level; severe facet joint disease at involved level; h/o discitis; osteoporosis, measured with DEXA; metastases; medical condition that required long-term use of medication that could affect bone quality and fusion rates. / •TDR with Prestige cervical disc prosthesis (n=276 enrolled, n=223 at 24-months; n=144 at 60 months)
•ACDF using allograft with plate fixation (n=265 enrolled, n=198 at 24 months; n=127 at 60 months) /
- RASP: NR
- CASP: NR
- CASP requiring treatment: Reported reoperation at adjacent levels for CASP
RCT comparing Kineflex/C disc to fusion
Coric (2011) / Randomized clinical trial
21 institutions
1:1 randomization
Conflict: Authors have consulted for, stock or direct ownership in, patent ownership in, received clinical or research support from, received statistical analysis and/or writing assistance from
SpinalMotion, Inc, Pioneer Surgical, Spinal Wave, DePuy Spine, Spinal Kinetics, Amedica, Replication Medical, K2M, Orthovita, LDR Spine, Nanovis. / N = 269
Male: 40.9%
Mean age: 43.8 ±7.6 (range 23-62) years
F/U: 87.0% (234/269)
Length of F/U:
24 months / Compare the clinical and radiographic outcomes of the Kineflex/C, a metal-on-metal C-TDR implant vs ACDF for the treatment of single-level spondylosis with radiculopathy in patients with a minimum of 2-year follow-up. / Inclusion: Age 18-60 yrs; symptomatic cervical degenerative disc disease/spondylosis at only 1 level from C3-C7 including ≥1 of the following: degenerated/ dark disc on MRI, disc height decreased by ≥1 mm when compared w/ adjacent levels on radiography, disc herniation on CT or MRI; 1 of the following radiculopathy symptoms in neck, 1 or both shoulders, &/or 1 or both arms: pain or paresthesias in a specific nerve root distribution from C3-C7, decreased muscle strength ≥1 level on 0–5 scale, abnormal sensation, including hyper- or hypo-esthesia; ≥1 of the following:≥6 mos of prior conservative treatment, presence of progressive symptoms (e.g., increasing numbness or tingling), signs of nerve root compression; NDI ≥40 (moderate disability);
appropriate for treatment using an anterior surgical approach; likely to return for all follow-up visits; willing & able to provide informed consent.
Exclusion: Marked cervical instability on resting lateral or flexion/extension radiograph (translation >3mm or >11° rotation compared w/ adjacent levels); nondiscogenic neck pain or nondiscogenic source of symptoms (e.g. tumor, rotator cuff injury); radiographic confirmation of severe facet disease or facet degeneration;
bridging osteophytes; <2° motion at index level; prior surgery at level to be treated, except laminotomy w/o accompanying facetotomy;
prior fusion at any cervical level; ≥1 neck surgery via anterior approach; previous trauma to the C3–7 levels resulting in compression or bursting; documented presence of free nuclear fragment at cervical levels other than study level; severe myelopathy (<3/5 muscle strength); any paralysis; recent history (≤ 6 mos) of chemical or alcohol dependence; active systemic infection; infection at site of surgery; prior disc space infection or cervical spine osteomyelitis; any terminal, systemic, or autoimmune disease; metabolic bone disease (e.g. osteoporosis, gout, osteomalacia, Paget disease); any disease, condition or surgery that may impair healing (e.g. insulin-dependent diabetes mellitus, active malignancy, history of metastatic malignancy); current or >6 month use of drug known to interfere with bone or soft-tissue healing; known metal allergy; arachnoiditis; current major mental illness diagnosis or symptoms (psychosis, major affective disorder, or schizophrenia); pregnancy at enrollment or planning to become pregnant; use of spinal stimulator at any cervical level prior to surgery;currently a prisoner; currently involved in spinal litigation that may influence the patient’s reporting of symptoms; participation in any other investigational drug, biological, or medical device study w/in the last 30 days prior to study surgery. / •Kineflex/C-TDR (n=136 enrolled; n=119 at F/U)
•ACDF with allograft and anterior plate (n=133 enrolled; n=115 at F/U) /
- RASP: Quantitative analysis of disc height and independent radiologist’s subjective assessments of extent of osteophyte formation and degree of endplate sclerosis, classified as none, mild, moderate, severe (based on Walraevens et al, Eur Spine J 18:358-369, 2009)*. For cases with pre-existing moderate RASP, a 1-grade change was required for classification as RASP; for other cases, a 2-grade increase in degeneration was classified as RASP.
- CASP: NR
- CASP requiring treatment: Reported reoperation at adjacent levels for CASP
None- negligible disc space narrowing, no osteophyte formation, no endplate sclerosis
Mild: <33% disc space narrowing, mild ostephyte formation, no endplate sclerosis
Moderate: 33-66% disc space narrowing, moderate osteophyte formation, mild to moderate endplate sclerosis
Severe: >66% disc space narrowing, severe osteophyte formation, moderate to severe endplate sclerosis
RCTs comparing ProDisc-C to fusion
Murrey (2009) / Randomized Clinical Trial
13 US investigational sites
1:1 randomization
Conflict: 4 authors report a financial relationship with Synthesis Spine that may indirectly relate to the subject of the research. / N = 209
Male: 45.5%
Mean age: ProDisc=42.1±8.4 years; ACDF=43.5±7.1 years
F/U: 96.5%
Lengh of F/U:
24 months / At the 2-year follow-up of a multicenter FDA IDE RCT, evaluate the safety and efficacy of the ProDisc-C TDR vs ACDF at a single level for the treatment of symptomatic C3-C7 cervical disc disease. / Inclusion: Age 18-60 years; symptomatic cervical disc disease in 1 vertebral level between C3-C7 causing neck or arm radicular pain and/or functional/neurological deficit with ≥1 of the following conditions confirmed by imaging: herniated nucleus pulposis, spondylosis with osteophytes, and/or loss of disc height; unresponsive to nonoperative treatment for ≥ 6 weeks or has the presence of progressive symptoms or signs of nerve root/spinal cord compression; neck disability index score ≥ 30%; psychosocially, mentally, and physically able to fully comply with protocol; signed informed consent.
Exclusion: >1 vertebral level requiring treatment; marked cervical instability on resting lateral or flexion-extension radiographs (translation >3mm, >11° rotational difference to that or either adjacent level); fused level adjacent to level being treated; radiographic confirmation of severe facet joint disease or degeneration; known allergy to cobalt, chromium, molybdenum, titanium or polyethylene; prior surgery at level to be treated; neck or arm pain of unknown etiology; clinically compromised vertebral bodies at the affected level secondary to trauma (e.g. radiographic appearance of fracture callus, malunion or nonunion); active local or systemic infection; severe spondylosis at level to be treated characterized by bridging osteophytes, >50% loss of disc height, <2° absence of motion; Paget’s disease, osteomalacia or metabolic bone disease; severe diabetes mellitus requiring daily insulin management; pregnant or interested in becoming pregnant in next 3 years; rheumatoid arthritis or other autoimmune disease; systemic disease including AIDS, HIV or hepatitis; osteoporosis (DEXA T score≤-2.5); taking medications known to potentially interfere with bone/soft-tissue healing; history of invasive malignancy except nonmelanoma skin cancer, unless treated with curative intent without clinical signs or symptoms of malignancy for>5 years. / •C-TDR with ProDisc-C (n=103 enrolled; n=101 at F/U)
•ACDF with allograft bone and anterior cervical plating (n=106 enrolled; n=100 at F/U) /
- RASP: NR
- CASP: NR
- CASP requiring treatment: Reported adjacent level reoperation at the 24-month follow-up
Nabhan (2007b) / Randomized controlled trial
Conflict: No funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. / N = 49
Male: 56.1%
Mean age: 44 years
F/U: 83.7% (41/49)
Length of F/U:
36 months / Investigate segmental motion following implantation of the ProDisc-C cervical spine disc prosthesis vs ACDF using a solis cage and anterior titanium plate 36 months after surgery. / Inclusion: Age 20-60 years; one-level cervical disc disease between C3-C7; Unresponsive to conservative treatment or presence or signs of nerve root compression with paresis; soft disc herniation; clinical evidence of radiculopathy; signed consent form
Exclusion: Marked cervical instability on resting or flexion-extension radiographs (translation >3mm, >11° rotational difference to that or either adjacent level); more than 1 level of pathology; myelopathy; radiographic confirmation of severe facet joint degeneration; hard disc disease; osteoporosis, infection, rheumatoid arthritis; spondylodiscitis and active infection; malignant disease; systemic disease, such as HIV, AIDS, hepatitis; known allergy to cobalt, chromium, molybdenum, titanium or polyethylene; traumatic injury of spine; pregnant or possible pregnancy in the next 3 years / •ProDisc-C (n=25 enrolled; n=20 at F/U)
•ACDF (n=24 enrolled; n=21 at F/U) /
- RASP: NR
- CASP: NR
- CASP requiring treatment: Reported adjacent level reoperation
Prospective cohort studies comparing motion-sparing devices to fusion
Kim (2009) / Prospective Cohort
Conflict: NR / N = 105
Male: 60.0%
Mean age:
Bryan=43.9 yrs;
ACDF=46.4 yrs
F/U: NR%
Mean F/U: 19 (range 12-40) months / Compare the clinical and radiologic outcomes of patients who underwent ACDF or Bryan cervical disc arthroplasty in single and bi-level cases and evaluate ongoing processes and underlying changes at the adjacent level during the follow-up period / Inclusion: Patients with symptomatic single or two-level cervical disc disease
Exclusion: NR / •Bryan disc (n=51)
•ACDF with autogenous bone and different types of anterior cervical plates or stand-alone cages (n=54) /
- RASP: Presence of new anterior or enlarging osteophyte, increase or new ≥30% narrowing of disc space, and/or calcification of the anterior longitudinal ligament in adjacent segment(s)
- CASP: NR
Maldonado (2011) / Prospective cohort
Conflict:
“None of the authors has any potential conflict of interest.” / N = 208
Male: 40.0%
Mean age: CDA=46.9±6.9 years; ACDF=46.5±6.4 years
F/U: 91.3% (190/208)
Length of F/U:
36 months / Evaluate the incidence of RASP in patients with cervical degenerative disc disease (DDD) who underwent cervical disc arthroplasty (CDA) compared to ACDF with a minimum follow-up of 3 years. / Inclusion:Age > 18 years, with single-level symptomatic DDD between C-3 and C-7 and intractable radiculopathy or/and myelopathy; unresponsive to ≥ 6 weeks of nonsurgical management or developed a new neurologic deficit secondary to myelopathy.
Exclusion: Evidence of cervical instability on dynamic flexion–extension radiographs or sagittal-plane angulation greater than +20° at a single level; previous surgery at the involved level; severe cervical spondylosis consisting of disc-space narrowing, osteophytosis, loss of cervical lordosis, uncovertebral joint hypertrophy, apophyseal
joint osteoarthritis, and/or diminished vertebral canal
diameter; osteoporosis with a T score below -2.5; medical condition that requires long-term use of medication that could affect bone quality and fusion rates. / •TDA with the Discocerv or Discover device (n=NR enrolled; n=85 at F/U)
•ACDF using cages with allograft bone (n=NR enrolled; n=105 at F/U) /
- RASP: Development of new anterior osteophyte formation or enlargement of existing osteophytes, increased or new narrowing of a disc space (> 30%), new or increased calcification of the anterior longitudinal ligament and the formation of radial osteophytes.
- CASP: NR
Nunley (2011) / Prospective Cohort from 3 RCTs at 2 institutions
Funding:
“No funding from any source was received for this project.”
Study population overlaps with that of the IDE trials; separate estimate of ASD frequency is not appropriate / N = 182
Male: 45%
Mean age: 44.5(range 22-67)
years
F/U: 93.4% (170/182)
Length of F/U: Median 38 (range 32-54) months / Compare the incidence of CASP at 3 and 4 years follow-up in 170 patients with one- and two-level cervical degenerative disc disease who received either TDA or ACDF in three different FDA prospective, randomized clinical trials / Inclusion:
One and/or two-level symptomatic cervical degenerative disc disease in skeletally mature patients, diagnosis of radiculopathy or myeloradiculopathy of the cervical spine in a specific nerve root distribution C3-C7, neck and/or arm pain VAS at least 30 mm on 100 mm scale, Neck Disability Index Score ≥ 30 points, unresponsive to conservative treatment for ≥ 6 months, absence of any medical condition that would interfere with the proposed surgery, subject provided informed consent and willing to comply with the protocol, no prior surgery at the index levels.
Exlusion:
Radiologic evidence of ASD, more than one immobile vertebral level from C1-C7 from any cause including but not limited to congenital abnormalities and osteoarthritic “spontaneous” fusions, previous trauma to the C3-C7 levels resulting in significant bony or discoligamentous
cervical spine injury, axial neck pain in the absence of other symptoms of radiculopathy or
myeloradiculopathy justifying the need for surgical intervention,radiographic confirmation of severe facet joint disease or degeneration, symptomatic DDD or significant cervical spondylosis at more than two levels, spondylolysis, marked cervical instability on resting lateral or flexion/extension radiographs
demonstrated by: translation greater than 3.5mm, and/or greater than 11° angular
difference to that of either adjacent level. / •TDA with Kineflex-C, Mobi-C or Advent Cervical Disc
(n=120 enrolled; n=113 at F/U)
•ACDF with allograft and anterior plates (n=62 enrolled; n=57 at F/U) /
- RASP: Subjects with recurrent cervical radiculopathy/myelopathy had MRI or CT scans that were analyzed for evidence of degeneration at the non-operated levels**. Electrophysiologic studies were then performed to rule-out peripheral nerve pathologies.
- CASP: CASP patients demonstrated clinico-radiologic presence of ASP AND received active intervention (subsequent medical management or surgery) for its management
Park SB (2012) / Prospective cohort
Conflict:
“None of the authors has any potential conflict of interest.” / N = 33
Male: 39%
Mean age: ADR=45 (range 17-61) years; ACDF=53 (range 38-66) years
F/U: 100% (33/33)
Length of F/U: ADR=28±5 months; ACDF= 30±6 months / Evaluate the effects of cervical artificial disc
replacement (ADR) and ACDF on other spinal alignment using changes of sagittal balance and curves of the thoracic and lumbar spines / Inclusion: Upper extremity
radiculopathy that was refractory to conservative treatments including medication and physiotherapy for ≥ 6 week;no previous spine surgery; ≥ 2-year follow-up
Exclusion: NR / •C-TDR (n=15)
•ACDF (n=18) /
- RASP: Development of new spondylotic changes in the adjacent vertebral bodies or a decrease of more than 10% in the height of adjacent discs
- CASP: NR
- CASP requiring treatment: Reported reoperation due to CASP
Prospective cohort study comparing motion-sparing devices to motion-sparing devices
Ryu (2010) / Prospective Cohort
Conflict: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. / N = 46
Male: 58.3%
Mean age:
Bryan=47.3 (range 37-62) yrs;
Prodisc=45.8 (range 29-61) yrs
F/U: 78.3% (36/46)
Mean F/U: 27.3±4.9 (range 24-40) months / Determine postoperative radiologic changes in discs and facets at index and adjacent levels following cervical arthroplasty using a Bryan or Prodisc-C device after a minimum follow-up of 2 years; to identify relationships between possible clinical factors and radiological changes; and to compare the results obtained using the 2 devices / Inclusion: Single-level degenerative cervical spine disease, underwent cervical arhtroplasty by a single surgeon using a Bryan disc (1st ½ of study) or a Prodisc-C (2nd ½ of study).
Exclusion: NR / •TDA with Bryan Disc (n=NR enrolled; n=19 subjects completed; n=38 levels completed)
•TDA with Prodisc-C (n=NR enrolled; n=17 subjects completed; n=34 levels completed) /
- RASP: Degenerative changes, spur formation and/or progression of facet arthrosis at adjacent levels on high-resolution CTs
- CASP: NR
*There is a significant loss to follow-up since, at the time of publication, not all subjects had reached the 60-month follow-up.